Bisphenol-A induces cellular transformation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells.
Bisphenol-A (BP-A) is a major component of epoxy, polycarbonate and other resins. For an assessment of in vitro carcinogenicity and related activity of BP-A, the abilities of this compound to induce cellular transformation and genetic effects were examined simultaneously using the Syrian hamster embryo (SHE) cell model. Cellular growth was reduced by continuous treatment with BP-A at doses > or = 100 microM. However, colony-forming efficiencies were not decreased significantly following treatment with up to 200 microM BP-A for 48 hr. Morphological transformation of SHE cells was induced by treatment of cells with BP-A at 50 to 200 microM for 48 hr. BP-A exhibited transforming activity at doses > or = 50 microM but was less active than the benzo[alpha]pyrene used as a positive control. Over the dose range that resulted in cellular transformation, treatment of SHE cells with BP-A failed to induce gene mutations at the Na+/K+ ATPase locus or the hprt locus. No statistically significant numbers of chromosomal aberrations were detected in SHE cells treated with BP-A. However, treatment of cells with BP-A induced numerical chromosomal changes in the near diploid range at doses that induced cellular transformation. 32P-Postlabeling analysis revealed that exposure of cells to BP-A also elicited DNA adduct formation in a dose-dependent fashion. Our results indicate that BP-A has cell-transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity.
Tsutsui
T
T
Department of Pharmacology, The Nippon Dental University, Tokyo, Japan.
Tamura
Y
Y
Yagi
E
E
Hasegawa
K
K
Takahashi
M
M
Maizumi
N
N
Yamaguchi
F
F
Barrett
J C
JC
D000782:Aneuploidy; D000818:Animals; D001559:Benzhydryl Compounds; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D006224:Cricetinae; D018736:DNA Adducts / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D008647:Mesocricetus; D010636:Phenols / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D018736:DNA Adducts; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds